Transfer and dynamics of uric acid in the pregnant rhesus monkey. I. Transplacental and renal uric acid clearances.

Data from the literature suggest that uric acid produced by the fetus could pass across the placenta and contribute to the observed increase in maternal plasma levels of uric acid in preeclamptic pregnancy. To investigate this hypothesis, fetal transplacental and renal uric acid clearances were estimated in 4 term pregnant rhesus monkeys by means of the steady infusion method using 14C-labeled uric acid. Allantoin clearances were determined in one pregnant monkey. Samples of maternal and fetal arterial blood were collected at regular intervals. The total amount of fetal urine produced during the experiment was collected at the end of the experiment. In addition, maternal endogenous renal uric acid and creatinine clearances were measured in 6 term pregnant monkeys. Fetal transplacental uric acid clearances appeared to be almost entirely limited by placental permeability and varied between 3.6 and 8.6 ml X min-1 X kg-1 of fetal weight; fetal renal clearances were between 0.11 and 0.20 ml X min-1 X kg-1. The allantoin clearances were found to be of the same magnitude. Maternal renal clearances of uric acid and creatinine were almost equal (mean 3.2 +/- 0.6 and 3.0 +/- 0.5 ml X min-1 X kg-1 of maternal weight, respectively). Extrapolation of these data to human preeclamptic pregnancy reveals that it is unlikely that fetal uric acid could significantly contribute to the maternal uric acid load.     

尿酸对胎盘系统A转运活性的影响

目的探讨尿酸对胎盘系统A氨基酸转运活性的影响。方法 2009年9月至2011年1月在中国医科大学附属盛京医院取无妊娠期并发症(如高血压、糖尿病等)与合并症的孕妇剖宫产分娩,体重正常的健康足月儿胎盘组织为研究对象。体外实验依据不同的尿酸质量浓度分为尿酸质量浓度178.5μmol/L组、297.5μmol/L组、416.5μmol/L组,以及不加尿酸的对照组。采用胎盘绒毛片段培养技术及同位素掺入技术对系统A的转运活性进行测定。结果 3种不同质量浓度尿酸组孵育2h后培养液中雌二醇质量浓度分别为(166.75±9.45)、(167.32±8.56)及(160.01±9.29)pmol/L,与对照组(170.03±11.32)pmol/L比较,差异均无统计学意义(P>0.05)。3组不同尿酸质量浓度组分别与对照组系统A的氨基酸转运活性比较,差异均有统计学意义(P均<0.05)。4组之间系统A的转运活性比较,差异有统计学意义(P均<0.05)。结论尿酸可能对胎盘系统A的氨基酸转运活性具有重要影响,这种影响具有浓度依赖性,而这一影响可能是高尿酸血症时引起低出生体重的重要机制之一。     

Placental and nonplacental drainage of the uterus in the pregnant rhesus monkey.

The proportion of placental to nonplacental drainage of the pregnant uterus of the anesthetized term rhesus monkey was assessed by means of a steady-state transplacental diffusion technique involving infusion of tritiated water at a constant rate into the fetal circulation and determination of the concentrations of radioactivity in the principal veins draining the uterus. No placental blood appeared to be drained through the hypogastric veins. There was considerable variation in the proportion of placental to nonplacental blood in each of the ovarian veins among the 6 animals studied. Ligation of one of the ovarian veins invariably resulted in a decrease in the transplacental clearance of tritiated water. It is concluded that blood samples from the ovarian veins of the pregnant rhesus monkey are generally not representative of the venous drainage of the placentas, which poses an important problem in the application of a diffusion equilibrium technique in this primate for measurement of uterine blood flow and consumption of gases based on the Fick principle.     

Second trimester amniotic fluid glucose,uric acid,phosphate, potassium,and sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight centiles

Objective: To study the evolution profile of amniotic fluid (AF) glucose, uric acid, phosphate, potassium, and sodium, in the second trimester of pregnancy, and explore the possible relations between the concentration of these components and maternal, as well as neonatal characteristics.

Methods: AF of 52 pregnant women was analyzed using an automatic multichannel analyzer. Maternal age, pre-pregnancy Body Mass Index (BMI), inter-pregnancy intervals, and smoking status were derived from questionnaires. Information on pregnancy and delivery was collected from medical records.

Results: Uric acid increased (r?=?0.423, p?r?=??0.590, p?r?=??0.314, p?r?=?0.460, p?r?=?0.274, p?=?0.052) and sodium (r?=?0.254, p?=?0.070) levels. Multiple linear regression indicated that mid-trimester AF uric acid and phosphate levels were significantly related to birth weight centiles (R^2?=?0.345, p?Conclusions: Our results suggest that: (a) AF phosphate levels reflect gestational age to a satisfactory extent, (b) maternal pre-pregnancy BMI is significantly correlated with AF uric acid concentration, and (c) in appropriate for gestational age infants, AF phosphate and uric acid levels may serve as potential biomarkers of birth weight centiles. Further studies on AF composition may help to unravel the biochemical pathways underlying fetal development and could offer insight on the potential impact of maternal nutritional management on fetal growth regulation.     

The relationship between serum uric acid and metabolic syndrome in premenopausal and postmenopausal women in the Jinchang Cohort

The aim of the study was to explore the association between serum uric acid (SUA) and metabolic syndrome (MetS) in premenopausal and postmenopausal women in the Jinchang Cohort. We studied 3808 female Jinchuan Nonferrous Metals Corporation workers aged 40–60 years. Cohort data from epidemiological surveys and medical exams were used. MetS was defined using the 2009 Joint Interim Society criteria. The relationship between SUA and MetS was evaluated using multiple logistic regression after adjusting for potential confounders. MetS and hyperuricemia were more prevalent in postmenopausal women than premenopausal ones (35.3% versus 15.2% and 9.2% versus 4.2%, respectively). Premenopausal and postmenopausal women with hyperuricemia had 2.81 (95% CI: 1.72–4.61) and 2.10 (95% CI: 1.44–3.08), respectively, times the odds of having MetS than their counterparts without hyperuricemia. Even within normal SUA quartiles, only premenopausal women in the highest and second-highest quartile had 3.57 (95% CI: 2.24–5.68) and 2.78 (95% CI: 1.71–4.50), respectively, times the odds of having MetS than those in the lowest quartile. Even in the normal range, the odds ratios for MetS increased gradually according to SUA levels in all women (P_trend?<_?0.001). In conclusion, there was a significant correlation between SUA levels and MetS, and the association was stronger in premenopausal women than postmenopausal ones.     

Combination of lipids and uric acid in mid-second trimester can be used to predict adverse pregnancy outcomes

Objective: The objective of this study was to evaluate the predictive values of lipids and uric acid in mid-second trimester for adverse pregnancy outcome. Methods: Lipids and uric acid concentrations were measured in 1000 healthy nulliparous women at 20 weeks of gestation. Pregnancy outcomes were followed-up. The odds ratios (OR) and 95% CI were estimated with unconditional logistic regression adjusting for maternal age and body mass index (BMI). Results: Women who had elevated triglyceride (TG) in the mid-second trimester experienced a 2.91-fold risk (95% CI 1.58–5.34) for preeclampsia and a 2.03-fold risk (95% CI 1.29–3.19) for gestation diabetes mellitus (GDM). Hyperuricemic women experienced a 1.99-fold risk (95% CI 1.16–3.40) for preeclampsia and a 2.34-fold risk (95% CI 1.44–3.83) for GDM, while women who had decreased high-density lipoprotein cholesterol (HDLc) experienced a 2.32-fold risk (95% CI 1.18–4.58) for preeclampsia, a 2.11-fold risk (95% CI 1.37–3.25) for GDM, and a 1.63-fold risk (95% CI 1.02–2.60) for delivering macrosomic newborns. These effects were concentration dependent, as risks increased with increasing TG quartiles and with decreasing HDLc quartiles. The result of the ROC analysis revealed that the sensitivity and specificity values for one marker alone was relatively low. But when combined TG, HDLc, uric acid, age and BMI together, the area under ROC curve increased to 0.71–0.77, sensitivity and specificity increased to 80–92% and 50–53%. Conclusion: The combination of these metabolic markers in mid-second trimester can be used to predict adverse pregnancy outcomes.     

Accuracy of serum uric acid in predicting complications of pre-eclampsia: a systematic review

BACKGROUND: Pre-eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre-eclampsia. OBJECTIVE: To determine the accuracy with which serum uric acid predicts maternal and fetal complications in women with pre-eclampsia. STUDY DESIGN: Systematic quantitative review of test accuracy studies. SEARCH STRATEGY: We conducted electronic searches in MEDLINE (1951-2004), EMBASE (1980-2004), the Cochrane Library (2004:4) and the MEDION database to identify relevant articles. A hand-search of selected specialist journals and reference lists of articles obtained was then carried out. There were no language restrictions for any of these searches. SELECTION CRITERIA: Two reviewers independently selected the articles in which the accuracy of serum uric acid was evaluated to predict maternal and fetal complications of pre-eclampsia. DATA COLLECTION AND ANALYSIS: Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standard. Summary likelihood ratios for positive (LR+) and negative LR(-) test results are generated for various threshold levels of uric acid. MAIN RESULTS: There were 18 primary articles that met the selection criteria, including a total of 3913 women and forty-one 2 x 2 tables. In women with pre-eclampsia, a positive test result of uric acid greater than or equal to a 350-micromol/l threshold predicted eclampsia with a pooled likelihood ratio (LR) of 2.1 (95% CI 1.4-3.5), while a negative test result had a pooled LR of 0.38 (95% CI 0.18-0.81). For severe hypertension as the outcome measure, the LRs were 1.7 (95% CI 1.3-2.2) and 0.49 (95% CI 0.38-0.64) for positive and negative test results, respectively, and for caesarean section the LRs were 2.4 (95% CI 1.3-4.7) and 0.39 (95% CI 0.20-0.76). For stillbirths and neonatal deaths the respective LRs were 1.5 (95% CI 0.91-2.6) and 0.51 (95% CI 0.20-1.3). For the prediction of small-for-gestational-age fetus, the pooled LRs were 1.3 (95% CI 1.1-1.7) and 0.60 (95% CI 0.43-0.83) for positive and negative results, respectively. AUTHOR'S CONCLUSION: Serum uric acid is a poor predictor of maternal and fetal complications in women with pre-eclampsia.     

Increased oxidant generation in the metabolism of hypoxanthine to uric acid and endothelial dysfunction in early-onset and late-onset preeclamptic women

Objective: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. Methods: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. Results: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. Conclusions: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.     

First versus second trimester mean platelet volume and uric acid for prediction of preeclampsia in women at moderate and low risk

Objective: To determine if second trimester mean platelet volume (MPV) and serum uric acid are reasonable predictors of preeclampsia (PE) or not, in patients at moderate and low risk. Methods: This prospective study was conducted on 9522 women at low or moderate risk for developing PE who underwent dual measurements of MPV and serum uric acid at late first trimester (10–12 weeks) and at second trimester (18–20 weeks) and subsequently divided into two groups; PE group (n = 286) who later developed PE and non-PE group (n = 9236). Test validity of MPV and serum uric acid was the primary outcome measure. Data were collected and analyzed. Results: Second trimester MPV is a good predictor for development of PE at a cutoff value of 9.55 fL with area under the curve (AUC) of 0.86, sensitivity of 95.2%, specificity of 66.7%, positive predictive value (PPV) of 87%, negative predictive value (NPV) of 85.7%, and accuracy of 86.7%. Second trimester serum uric acid is a good predictor for development of PE at a cutoff value of 7.35 mg/dL, with AUC of 0.85, sensitivity of 95.2%, specificity of 55.6%, PPV of 83.3%, NPV of 83.3%, and accuracy of 83.3%. Combination of both tests has a sensitivity of 100%, specificity of 22.2%, PPV of 75%, NPV of 100%, and accuracy of 76.7%. Conclusion: Second trimester MPV and serum uric acid alone or in combination could be used as a useful biochemical markers for prediction of PE based on their validity, simplicity, and availability.     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.     

Computational model of the pregnant occupant: predicting the risk of injury in automobile crashes

OBJECTIVE: The goal of this study was to create a computational model of the pregnant occupant of a motor vehicle to predict fetal outcome in crashes. STUDY DESIGN: A finite element uterine model of a 7-month pregnant woman was created and integrated into a multibody human model. Unrestrained, three-point belt, and three-point belt plus airbag tests were simulated at speeds that ranged from 13 to 55 km per hour. RESULTS: Peak uterine strain, as determined by the model, correlated well with the risk of fetal death, as determined by investigations of car crashes. The strain in the uterine wall exceeded the limits of the tissue in simulations of no restraint at 35 km per hour and three-point belt tests at 45 and 55 km per hour. The safest restraint for the pregnant driver is the combination three-point belt and airbag. CONCLUSION: The model is a good first step toward the prediction of the risk of fetal death and verified experimental findings that note the importance of proper restraint use for the pregnant occupant.     

Serum levels of uric acid may have a potential role in the management of immediate delivery or prolongation of pregnancy in severe preeclampsia

ABSTRACT

Objective

To investigate the biomarker(s) that could affect the decision for immediate or delayed delivery in severe preeclampsia.